PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

A 'rocking' receptor: Crucial brain-signaling molecule requires coordinated motion to turn on

Study could help yield new drugs for brain disorders

2013-08-07
(Press-News.org) Johns Hopkins biophysicists have discovered that full activation of a protein ensemble essential for communication between nerve cells in the brain and spinal cord requires a lot of organized back-and-forth motion of some of the ensemble's segments. Their research, they say, may reveal multiple sites within the protein ensemble that could be used as drug targets to normalize its activity in such neurological disorders as epilepsy, schizophrenia, Parkinson's and Alzheimer's disease.

A summary of the results, published online in the journal Neuron on Aug. 7, shows that full activation of so-called ionotropic glutamate receptors is more complex than previously envisioned. In addition to the expected shape changes that occur when the receptor "receives" and clamps down on glutamate messenger molecules, the four segments of the protein ensemble also rock back and forth in relation to each other when fewer than four glutamates are bound.

"We believe that our study is the first to show the molecular architecture and behavior of a prominent neural receptor protein ensemble in a state of partial activation," says Albert Lau, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine.

Glutamate receptors reside in the outer envelope of every nerve cell in the brain and spinal cord, Lau notes, and are responsible for changing chemical information — the release of glutamate molecules from a neighboring nerve cell — into electrical information, the flow of charged particles into the receiving nerve cell. There would be sharply reduced communication between nerve cells in our brains if these receptors were disabled, he added, and thought and normal brain function in general would be severely compromised. Malfunctioning receptors, says Lau, have been linked with numerous neurological disorders and are therefore potential targets for drug therapies.

Lau explained that each glutamate receptor is a united group of four protein segments that has a pocket for clamping down on glutamate like a Venus fly trap snaring a bug. Below the glutamate-binding segments are four other segments embedded in the cell's outer envelope to form a channel for charged particles to flow through. When no glutamates are bound to the receptor, the channel is closed; full activation of the receptor and full opening of the channel occur when four glutamates are bound, each to a difference pocket.

Previously, Lau says, investigators thought that the level of receptor activation simply corresponded to the degree to which each glutamate-binding segment changed shape during the glutamate-binding process. Using a combination of computer modeling, biophysical "imaging" of molecular structure, biochemical analysis and electrical monitoring of individual cells, the researchers teased apart some of the steps in between zero activation and full activation. They were able to show that the four glutamate-binding segments, in addition to clamping down on glutamate, also rock back and forth in pairs when fewer than four glutamates are bound.

"It isn't clear yet how this rocking motion affects receptor function, but we now know that activation depends on more than how much each glutamate-binding segment clamps down," says Lau. Previous development of drugs targeting the receptor focused on the four glutamate-binding pockets. "Our discovery of this molecular motion could aid the development of drugs by revealing additional drug-binding sites on the receptor," he adds.



INFORMATION:



Other authors of the report include Héctor Salazar, Valentina Ghisi and Andrew Plested of the Leibniz-Institut für Molekulare Pharmakologie, and Lydia Blachowicz and Benoît Roux of the University of Chicago.

This work was supported by grants from the National Institute of General Medical Sciences (GM094495, GM062342), NeuroCure and the Human Frontier Science Program.



ELSE PRESS RELEASES FROM THIS DATE:

Scripps Research Institute scientists find key signal that guides brain development

2013-08-07
LA JOLLA, CA – August 7, 2013 – Scientists at The Scripps Research Institute (TSRI) have decoded an important molecular signal that guides the development of a key region of the brain known as the neocortex. The largest and most recently evolved region of the brain, the neocortex is particularly well developed in humans and is responsible for sensory processing, long-term memory, reasoning, complex muscle actions, consciousness and other functions. "The mammalian neocortex has a distinctive structure featuring six layers of neurons, and our finding helps explain how this ...

Psychological adaptation to urbanization, technology reflected in word usage over last 200 years

2013-08-07
New research shows that as culture has evolved over the last two centuries – with increasing urbanization, greater reliance on technology, and widespread availability of formal education – so has human psychology. The findings are forthcoming in Psychological Science, a journal of the Association for Psychological Science. "This research shows that there has been a two-century long historical shift towards individualistic psychological functioning adapted to an urban environment and away from psychological functioning adapted to a rural environment," says psychological ...

Changes in language and word use reflect our shifting values, UCLA psychologist reports

2013-08-07
A new UCLA analysis of words used in more than 1.5 million American and British books published between 1800 and 2000 shows how our cultural values have changed. The increase or decrease in the use of certain words over the past two centuries — a period marked by growing urbanization, greater reliance on technology and the widespread availability of formal education — reveals how human psychology has evolved in response to major historical shifts, said Patricia Greenfield, a distinguished professor of psychology at UCLA and the author of the study. For instance, ...

AAAS report shows steady escalation of destruction in Aleppo

2013-08-07
In Syria's largest city, Aleppo, damage to buildings and infrastructure steadily increased over a ten-month period ending in May 2013, according to a new analysis by AAAS of high-resolution satellite images. Virtually all of the destruction appears to be in rebel-controlled or contested areas, and a substantial amount is in Aleppo's Ancient City, a UNESCO World Heritage Site. Aleppo has been the site of ongoing conflict since July 2012. Since then, the city has experienced a nearly constant rate of damage to its physical structures, at about three incidents per day on ...

The team of proteins that could have implications for the fight against cancer

2013-08-07
Researchers at Warwick Medical School have identified the key role played by a team of proteins in the process of mitosis. Working out how to control them may give scientists a way to destroy cancerous cells. The study, led by Professor Steve Royle and published in The Journal of Cell Biology, highlights the role of a newly identified team of proteins, TACC3-ch-TOG-clathrin, in forming inter-microtubule bridges that stabilise the kinetochore fibres (K-fibres) used in mitosis. When a cell divides, it produces a mitotic spindle which then makes sure that the chromosomes ...

Brain activation when processing Chinese hand-radicals

2013-08-07
A number of studies in which patients with lesions to frontal pre-motor areas are included have identified deficits in action comprehension. In addition, imaging studies have revealed the activation of brain areas associated with perception or action during tasks involving reading of words with related semantic meaning. For example, the mere passive reading of action verbs such as kick, pick and lick has been found to activate areas of the sensory-motor cortex associated with the legs, hands and face, respectively. To investigate the semantic processing of Chinese radicals ...

Mechanism underlying cisplatin-induced ototoxicity

2013-08-07
Studies have shown that calpain participates in gentamicin-, neomycin- and kanamycin-induced inner ear cell apoptosis. Cisplatin has been shown to be an anticancer drug. However, cisplatin can lead to severe ototoxicity, induce cochlear cell apoptosis, and result in hearing decrease or loss, which limits the application of cisplatin in a clinical setting to a certain degree. A recent study by Liang Chang and colleagues from Jinzhou Central Hospital established a BALB/c mouse model of cisplatin-induced ototoxicity to detect the susceptibility to cisplatin-induced ototoxicity. ...

Caffeine 'traffic light': Do you want to know how much caffeine is in your drink?

2013-08-07
A team of researchers led by Prof. Young-Tae Chang from National University of Singapore and Prof. Yoon-Kyoung Cho from Ulsan National Institute of Science and Technology (UNIST), Korea, developed a fluorescent caffeine detector and a detection kit that lights up like a traffic light when caffeine is present in various drinks and solutions. The research work was published in Scientific Reports (Nature Publishing Group) on July 23, 2013. Caffeine drinks are ubiquitous and it would be unimaginable for many of us to go a day without caffeine. But certainly one begins to ...

Diamonds are a laser scientist's new best friend

2013-08-07
Once a James Bond fantasy, diamond-based lasers are now becoming a reality. Ground-breaking research is harnessing the unique properties of diamonds to develop a new generation of lasers that could lead to many benefits, from better treatment of skin complaints and diabetes-related eye conditions to improved pollution monitoring and aeronautical engineering. A University of Strathclyde team has developed a new type of high-performance, ultra-versatile Raman laser* that harnesses diamonds to produce light beams with more power and a wider range of colours than current ...

Trust thy neighbor

2013-08-07
Increases in population size may lead to a breakdown in social trust, according to Jordan Smith from North Carolina State University in the US. As local populations grow, local elected officials and national news media become less trusted, compared with friends and family, local churches and civic institutions. This 'trust deficit' has implications for long-term environmental and community planning. Smith's study is published online in Springer's journal Human Ecology. Smith studied three southern Appalachian mining communities during a period of change, amid growing ...

LAST 30 PRESS RELEASES:

Identification of chemical constituents and blood-absorbed components of Shenqi Fuzheng extract based on UPLC-triple-TOF/MS technology

'Glass fences' hinder Japanese female faculty in international research, study finds

Vector winds forecast by numerical weather prediction models still in need of optimization

New research identifies key cellular mechanism driving Alzheimer’s disease

Trends in buprenorphine dispensing among adolescents and young adults in the US

Emergency department physicians vary widely in their likelihood of hospitalizing a patient, even within the same facility

Firearm and motor vehicle pediatric deaths— intersections of age, sex, race, and ethnicity

Association of state cannabis legalization with cannabis use disorder and cannabis poisoning

Gestational hypertension, preeclampsia, and eclampsia and future neurological disorders

Adoption of “hospital-at-home” programs remains concentrated among larger, urban, not-for-profit and academic hospitals

Unlocking the mysteries of the human gut

High-quality nanodiamonds for bioimaging and quantum sensing applications

New clinical practice guideline on the process for diagnosing Alzheimer’s disease or a related form of cognitive impairment or dementia

Evolution of fast-growing fish-eating herring in the Baltic Sea

Cryptographic protocol enables secure data sharing in the floating wind energy sector

Can drinking coffee or tea help prevent head and neck cancer?

Development of a global innovative drug in eye drop form for treating dry age-related macular degeneration

Scientists unlock secrets behind flowering of the king of fruits

Texas A&M researchers illuminate the mysteries of icy ocean worlds

Prosthetic material could help reduce infections from intravenous catheters

Can the heart heal itself? New study says it can

Microscopic discovery in cancer cells could have a big impact

Rice researchers take ‘significant leap forward’ with quantum simulation of molecular electron transfer

Breakthrough new material brings affordable, sustainable future within grasp

How everyday activities inside your home can generate energy

Inequality weakens local governance and public satisfaction, study finds

Uncovering key molecular factors behind malaria’s deadliest strain

UC Davis researchers help decode the cause of aggressive breast cancer in women of color

Researchers discovered replication hubs for human norovirus

SNU researchers develop the world’s most sensitive flexible strain sensor

[Press-News.org] A 'rocking' receptor: Crucial brain-signaling molecule requires coordinated motion to turn on
Study could help yield new drugs for brain disorders